3-phenyl-2-propeneamine derivatives, their preparation and compositions containing them

Abstract

The invention provides compounds of formula: ##STR1## in which R=H, halogen, alkyl, alkyloxy, alkythio, NH 2 , alkylamino, dialkylamino or CF 3 , R 3 =H or alkyl, either R 4 and R 5 =H and R 1 and R 2 =H or alkyl, optionally substituted by alkenyl (2 to 4 C) or alternatively R 1 and R 2 form together a saturated heterocyclic ring containing 4 to 7 ring members and optionally containing another heteroatom such as O, S or N optionally substituted by alkyl, or R 4 =H, R 1 =H or alkyl and R 2 and R 5 together form an alkylene (3 to 4 C) radical and (i) either A=alkyl or phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, NH 2 , alkylamino, dialkylamino, NO 2 or CF 3 or alternatively A=pyridyl, benzyl or cycloalkyl (3 to 6C), Y=S, SO or SO 2 or a radical: ##STR2## in which R 6 =H or alkyl and R 7 =H or alkylcarbonyl, alkyloxycarbonyl, alkylaminocarbonyl or benzoyl, optionally substituted by one or two halogen, alkyl, alkyloxy, alkylthio, NH 2 , alkylamino, dialkylamino, NO 2 or CF 3 groups, (ii) or Y and A together form a 1-hydroxycycloalkyl radical, the ring of which contains 5 or 6 C, optionally joined to a benzene ring, it being understood that the alkyl radicals and alkyl parts contain 1 to 4 C as a straight or branched chain, and that the invention relates to all the possible geometric and optical isomers as well as their mixtures. These compounds are useful as antidepressants.

We claim: 
     
       1. A 3-phenyl-2-propeneamine of the formula: ##STR36## in which R denotes hydrogen, halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino or trifluoromethyl, R 3  denotes hydrogen or alkyl; either R 4  and R 5  each denote hydrogen and R 1  and R 2 , which are identical or different, each denote hydrogen or alkyl which is unsubstituted or substituted by alkenyl of 2 to 4 carbon atoms, or R 1  and R 2  form together with the nitrogen atom to which they are linked or saturated heterocyclic radical of 4 to 7 ring atoms optionally containing another heteroatom selected from the group consisting of oxygen, sulphur or nitrogen which is unsubstituted or substituted by alkyl; or R 4  denotes hydrogen, R 1  denotes hydrogen or alkyl and R 2  and R 5  together form an alkylene radical 3 or 4 carbon atoms; and either (i)A denotes phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino, nitro and trifluoromethyl, pyridyl, benzyl or cycloalkyl of 3 to 6 carbon atoms, and Y denotes sulphur, sulphinyl, sulphonyl or a radical of the formula: ##STR37## in which R 6  denotes hydrogen or alkyl and R 7  denotes hydrogen, alkylcarbonyl, alkyloxycarbonyl, alkylaminocarbonyl or benzoyl, which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino, nitro and trifluoromethyl, or (ii) Y and A together form a 1-hydroxycycloalkyl radical the ring of which contains 5 or 6 carbon atoms, optionally joined to a benzene ring; and its pharmaceutically acceptable salts, the aforesaid alkyl radicals and alkyl parts containing 1 to 4 carbon atoms each as a straight or branched chain, in the form of any geometric or optical isomer or any mixture thereof. 
     
     
       2. A 3-phenyl-2-propeneamine according to claim 1 in which R denotes hydrogen, halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino or trifluoromethyl; R 3  denotes hydrogen or alkyl; and either R 4  and R 5  denote hydrogen and R 1  and R 2  which are identical or different, each denote hydrogen or alkyl unsubstituted or substituted by alkenyl of 2 to 4 carbon atoms, or R 1  and R 2  together form with the nitrogen atom to which they are linked a saturated heterocyclic radical containing 4 to 7 ring atoms; or R 4  denotes hydrogen, R 1  denotes hydrogen or alkyl and R 2  and R 5  together form alkylene of 3 or 4 carbon atoms; and either (i) A denotes phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, and trifluoromethyl, pyridyl, benzyl or cycloalkyl of 3 to 6 carbon atoms, Y denotes sulphur, sulphinyl, or a radical of formula: ##STR38## in which R 6  denotes hydrogen or alkyl and R 7  denotes hydrogen, alkylcarbonyl, alkyloxycarbonyl, benzoyl or alkylaminocarbonyl, or (ii) Y and A together form a 1-hydroxycycloalkyl radical the ring of which contains 5 or 6 carbon atoms, optionally combined with a benzene, ring, in the Z or E form, the said alkyl radicals and alkyl parts containing 1 to 4 carbon atoms each, as a straight or branched chain, and its pharmaceutically acceptable salts.   
     
     
       3. A 3-phenyl-2-propeneamine according to claim 1 in which R denotes hydrogen, halogen, alkyl, alkyloxy, alkylthio, amino, alkylamino, dialkylamino or trifluoromethyl, R 3  denotes hydrogen, R 4  and R 5  denote hydrogen, and R 1  and R 2 , which are identical or different, each denote hydrogen or alkyl unsubstituted or substituted by alkenyl of 2 to 4 carbon atoms; and A denotes phenyl, which is unsubstituted or substituted by one or two substituents chosen from halogen and alkyl, pyridyl or cycloalkyl of 3 to 6 carbon atoms, Y denotes a sulphur atom, or a radical of formula: ##STR39## in which R 6  denotes hydrogen and R 7  denotes hydrogen or alkylcarbonyl, in the Z form, the said alkyl radicals and alkyl parts containing 1 to 4 carbon atoms each as a straight or branched chain, and its pharmaceutically acceptable salts. 
     
     
       4. A compound according to claim 1 which is 4-dimethylamino-1,2-diphenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts. 
     
     
       5. A compound according to claim 1 which is 4-methylamino-1,2-diphenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts. 
     
     
       6. A compound according to claim 1 which is 1-(3-fluorophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts. 
     
     
       7. A compound according to claim 1 which is 1-(3-chlorophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts. 
     
     
       8. A compound according to claim 1 which is 1-(3-bromophenyl)-4-dimethylamino-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts. 
     
     
       9. A compound according to claim 1 which is 4-dimethylamino-1-(2-methylphenyl)-2-phenyl-2-buten-1-ol-(Z) and its pharmaceutically acceptable salts. 
     
     
       10. A pharmaceutical composition comprising a compound as claimed in claim 1 as a base or a pharmaceutically acceptable salt thereof in combination with one or more compatible, pharmaceutically acceptable diluents or adjuvants.